The development of nuclear magnetic resonance (NMR) spectroscopy for biological diagnostics was a discovery welcomed by those who analyze living systems. An extensive discussion of the NMR techniques and application to living systems may be found in commonly assigned co-pending applications Ser. No. 90,400, filed Sep. 4, 1986, now U.S. Pat. No. 4,839,352 and Ser. No. 106,114, filed Oct. 7, 1987, now U.S. Pat. No. 4,998,976 all of which are incorporated herein by reference as if set forth herein fully.
It is understood that techniques for NMR spectroscopy rely upon identifying characteristic concentrations and distributions of protons in a test sample. The sample is subjected to pulses of electromagnetic energy while the sample is positioned within a uniform magnetic field. A typical such pulse used to analyze protons is at 50MHz for 10 microseconds, although frequencies and pulse widths will vary. Data characteristics of the proton population received while the sample is under the influence of the magnetic field yield valuable information about living systems. Sensors are provided for sensing the rates of relaxation or energy release of the protons and generating a signal in the time domain commonly called the free induction decay (FID) signal. This signal can be analyzed with a Fourier transform to develop a spectrum of signals in the frequency domain. Analytical means must then be provided for receiving and analyzing the signals emitted, discriminating between various peaks, comparing the amplitude or height of various peaks, and/or normalizing the analysis by reference to a standard sample so as to obtain the concentration of constituents in the tested materials. It has been found that the characteristic resonant frequency of a nucleus depends to a very small, but measurable, extent upon its chemical environment. It is found, for instance, that the protons of water do not absorb at quite the same frequency as those of mineral oil, the difference being only a few parts per million.
Thus, a number of different signals may be obtained in one NMR reading. It is imperative that the NMR signals in question be strong enough to yield signals above the receiver noise and narrow enough to be distinguishable from one another. Various operations are used to better the signal-to-noise ratios. Such improvement can be obtained by signal averaging techniques such that with the accumulation of N-scans, the net increase of the S/N conditions will be N since the noise is random. Thus, if four data averagings are performed, the S/N ratio will increase by a factor of 2.
While the proton is the most sensitive nucleus to excite, it is also the most abundant and therefore yields more complex spectra and additionally yields a large solvent peak in aqueous solutions. Such a large peak makes it difficult to observe weaker signals within the sample. When the FID time domain signal has been transformed by the Fourier analysis into a frequency domain signal, the frequency spectrum designating, for example, the water as a peak may yield a very large peak. When the signals are run through an amplifier, the large water peak saturates the amplifier and the smaller signals cannot be properly analyzed.
There have been a number of systems in an attempt to eliminate the effect of the water peak. One is known as WEFT and the acronym stands for Water Eliminated Fourier Transform NMR Spectroscopy. This method is based on the inversion-recovery technique for the measurement of the well-known spin-lattice relaxation time, T.sub.1. The technique involves the inversion of the magnetization, in some cases both the solvent and solute resonances, by a 180.degree. pulse followed after an interval .tau. by a 90.degree. sampling pulse to measure the regrowth of the magnetization toward equilibrium. It is known that when .tau.=0.693T.sub.1 (solvent), the recovering solvent magnetization passes through zero. If the solute T.sub.1 is substantially shorter than that of the solvent, a 90.degree. pulse at this time, followed by the acquisition of the signal, will provide a spectrum of the solute without that of the solvent. After an interval of 5T.sub.1 (solvent), the pulse sequence may be repeated. It is possible to suppress the solvent resonance 1000-fold with this method.
Another method that is frequently employed for the selective excitation of solute resonances without exciting the solvent is the Redfield "2-1-4" pulse. In this case, the interval from the center of a function to the first null corresponding to the difference between the transmitter frequency and the solvent frequency is given by 1/.tau., the reciprocal of the pulse width .tau.. If, for example, .tau. is 500 microseconds (a rather long or "soft" pulse), this frequency is 2000Hz. A nucleus resonating at 2000Hz from the transmitter frequency will not experience any net flipping by the RF field and so will not appear in the spectrum. Because a square wave pulse in the form of ##EQU1## is a function that crosses the null very abruptly, effective suppression of a solvent resonance requires careful adjustment of the transmitter frequency and the pulse width.
Other techniques are used to attempt to suppress solvent peaks. However, with all of these techniques, solute resonances at or near the solvent resonance will also inevitably be suppressed. Further, the techniques are complicated and difficult to perform and require exacting adjustments in order to achieve effective suppression.
The present invention overcomes the disadvantages of the prior art by providing an apparatus and method for suppressing any unwanted characteristic resonance in a preselected manner. It is well known that when the FID time domain signal is generated by the NMR circuit, a fast Fourier transform (FFT) of the FID signal results in a frequency domain spectrum illustrating the peaks having varying amplitudes for the various constituents in the sample. In such cases, as explained previously, one of the peaks will be much stronger than the other peaks and, for example, in a sample with a water solvent, the peak representing the water solvent is usually very strong and overshadows all of the other peaks. If it is desired to remove this peak, shown in the time domain spectrum on a display system, an operator using a keyboard and a microprocessor simply designates the portion or portions of the frequency domain spectrum that are to be eliminated. Since the microprocessor memory stores in digital form the data that is being displayed as the frequency domain spectrum, it is relatively simple for the microcomputer to delete from the displayed frequency domain spectrum those frequencies that one desires to eliminate. Thus, the resulting frequency domain spectrum displayed is a desired spectrum, not the actual spectrum.
This desired frequency domain spectrum is then operated on by a reverse fast Fourier transform function to generate an FID signal in the time domain that would represent such a desired frequency domain signal before the FFT transform. This FID signal is then digitized and converted into an analog signal which is used to pulse the sample under test with a typical NMR device. A new FID time domain signal is obtained and passed through a fast Fourier transform device to transform the time domain signal into a frequency domain signal. The frequency domain signal will not have the peaks that were previously selected for removal. Thus, the remaining peaks can be passed through linear amplifiers as necessary to obtain further analysis of those signals.
Further, instead of eliminating just one particular frequency in the frequency domain spectra, blocks of frequencies may be removed. For instance, if the frequency domain spectrum has a width of 400Hz, one could elect to eliminate the area including the first 40Hz, the eighth 20Hz block, and the tenth 30Hz block. If the frequency domain spectrum extended from Hz to 400Hz, for example, one could delete a block of data from Hz to 40Hz, a second block of data from 141Hz to 160Hz, and a third block of data from 271Hz to 300Hz. Clearly, any other one block or multiple blocks of data could be eliminated from the frequency domain spectrum in this manner. Using this procedure, the high peaks in frequency domain spectra can be eliminated thus allowing the smaller peaks to be passed through a linear amplifier to obtain more precise information and better analysis.
Thus, it is the preferred object of the present to generate an NMR signal having a preselected frequency domain spectrum for constituents in a given sample.
It is another object of the present invention to modify an existing frequency domain spectrum into a desired frequency domain spectrum, converting the desired spectrum to analog signals, and pulsing an NMR device with the analog signals to obtain an FID signal which, when transformed into a frequency domain signal, eliminates preselected, undesired solvent peaks.
It is also an object of the present invention to generate a frequency spectrum representing the constituents in a test sample, removing from the frequency domain spectrum predetermined blocks of frequencies which are undesirable, performing a reverse FFT transform on the modified frequency domain spectra to obtain a new FID signal, digitizing the FID signal, changing the digitized signal to an analog signal, pulsing the test sample with the modified signal to obtain a new FID signal, and performing a fast Fourier transform on the newly obtained FID signal to obtain the desired frequency domain spectra having the undesirable frequencies eliminated.